Updates in Treatment of
Hepatitis C
Gene LeSage, MD, FACP, AGAF
Objectives
• HCV epidemiology, risk factors, diagnosis and
prognosis
• Interferon (IFN) and Ribavirin (RBV) based
therapy
• Direct acting anti-viral (DAA) therapies
HCV Epidemiology
• Nearly 3% of worldwide population has chronic HCV infection[1,2]
– Most common blood-borne infection in United States[3]
• Up to 75% unaware of HCV infection until liver disease or cancer
develops many yrs later[4]
• HCV infection associated with multiple disease processes[5]
– Including liver disease, diabetes, B-cell proliferative disorders,
depression, and cognitive disorders
• Diminishing HCV infection rates, morbidity through prevention an
important ongoing public health initiative
1. Lavanchy D. Liver Int. 2009;29:74-81. 2. Shepard CW, et al. Lancet Infect Dis. 2005;5:558-567.
3. IOM. Hepatitis and Liver Cancer. NA Press. 2010. 4. Mitchell AE, et al. Hepatology. 2010;51:729-733.
5. Jacobson IM, et al. Clin Gastroenterol Hepatol. 2010;8:1017-1029.
•
•
•
•
•
•
•
•
Hepatitis C Virus Infection
Population at Risk
Transfusion of blood products before 1992
Intravenous drug use
Nasal inhalation of cocaine
Chronic renal failure on dialysis
Incarceration
Occupational exposure to blood products
Transplantation of an organ/tissue graft from an HCVpositive donor
Body piercing and potentially tattoo
Centers for Disease Control and Prevention. Hepatitis C fact sheet. Available at:
http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm. Accessed February 1, 2006.
Routes of Transmission
Injecting drug use 60%
Sexual 15%
Transfusion 10%
(before screening)
Occupational 4%
Other 1%*
Unknown 10%
* Nosocomial; iatrogenic; perinatal
Source: Centers for Disease Control and Prevention
Hepatitis C Virus
Diagnostic Testing
Diagnostic Test Type
Specifications
Serologic
Virologic
Mode of detection
Antibodies
Virus
Sensitivity
> 95%
> 98%
Specificity
Variable
> 98%
Detection postexposure
2-6 months
2-6 weeks
Use
Screening
Confirmation
HCV Infection - Liver Biopsy
• Only test that can accurately assess
– Severity of inflammation
– Degree of fibrosis
• Determines the following
– Risk for developing cirrhosis in future
– Need for therapy
– Need for ongoing therapy when initial treatment has failed
Hepatitis C Virus
Response to Acute Infection
200
+
ALT (IU/l)
150
HCV RNA
+ Resolution
100
Chronic
50
0
0
6
12
Month
Illustration by Mitchell L. Shiffman, MD.
18
24
Prevalence of Anti-HCV, United States, 1999-2002
(NHANES)
Overall prevalence: 1.6% (4.1 million)
Born ~1945-1965
Prevalence of anti-HCV
8%
7%
Men
6%
Women
5%
4%
3%
2%
1%
Age Group (years)
Armstrong et al. AASLD 2004.
55+
50-54
45-49
40-44
35-39
20-34
6-19
ALL
0%
HCV to HCC Pyramid
1%
HCC
(1%–3%/y)
Cirrhosis
15%
(10%–30%/y)
25 y
Chronic Hepatitis
HCV Infection
Graphic courtesy of Dr. H.B. El-Serag.
90%
(60%–95%/y)
100%
Liver Cancer Has the Fastest Growing
Death Rate in the United States
Trends in US Cancer Mortality Rates
All Other Cancers
(Average)
Corpus & Uterus, NOS
Testis
Lung & Bronchus (Female)
Esophagus
Thyroid
Liver
-2
-1.5
-1
-0.5
0
0.5
Annual Percent Change (1994–2003)
1
1.5
NOS = not otherwise specified.
National Cancer Institute. Seer Summary Figures and Tables. Available at:
http://seer.cancer.gov/csr/1975_2003/results_merged/topic_graph_trends.pdf. Accessed on
October 17, 2008.
2
Chronic Hepatitis C Infection
Progression to Cirrhosis
Mild
15%-33%
Moderate
Severe
Cirrhosis A
20%-33%
Cirrhosis C
HCC
0
10
20
30
Years
Shiffman ML. Viral Hepatitis Rev. 1999;5:27-43.
40
50
Established Risk Factors for Progression
of Fibrosis and Cirrhosis
 Male gender
 Longer duration of infection
 Age >40 years at time of infection
 Alcohol excess
 >50 gm/day - men
 >30 gm/day - women
 Persistently elevated ALT levels
 HIV, HBV coinfections
 Organ transplantation
Poynard T, Lancet 1997 349:825-32
Mathurin P, Hepatology 1998 27:868-72
Benhamou J, Hepatology 1999 30:1054-8
Newly-Recognized Risk Factors for HCV
Disease Progression
 Menopausal status
 Cannabis
 Insulin resistance
 Obesity, metabolic syndrome
Chronic HCV Infection
Normal vs Elevated Serum ALT
Portal
26%
Bridging
6%
No
fibrosis
23%
Bridging
13%
Portal
20%
Cirrhosis
18%
Cirrhosis
6%
Mild
39%
Normal ALT
Shiffman ML, et al. J Infect Dis. 2000;182:1595-1601.
No
fibrosis
16%
Elevated ALT
Mild
33%
HCV RNA effect on Liver Histology & Fibrosis
 Serum HCV RNA does not correlate with level of fibrosis
Log HCV RNA
(copies/mL)
8
Genotype
1
2
3
4
6
4
2
0
No
Fibrosis
Portal
Fibrosis
Ferreira-Gonzalez A, et al. Semin Liver Dis. 2004;24:9-18.
Bridging Cirrhosis
Fibrosis
HCV and Alcohol
100
Cirrhosis (%)
80
60
HCV
HCV + alcohol
40
20
0
10
20
30
40
Years Following Exposure
Excessive alcohol intake characterized as > 40 g/day for women and > 60 g/day for men.
Wiley TE, et al. Hepatology. 1998:28:805-809.
Past and Future (Estimated) US Incidence
and Prevalence of HCV Infection
Decline among IDUs
Overall incidence
Infections
per 100,000
150
100
50
0
1960
1970
1980
1990
Graphic courtesy of Centers for Disease Control and Prevention.
2000
2010
2020
2030
The Changing Face of HCV in the US
6,000,000
Ever HCV infected
All chronic HCV
Acute HCV infection
Cirrhosis
Peak
incidence
Persons (n)
5,000,000
Peak
cirrhosis
4,000,000
3,000,000
2,000,000
1,000,000
0
1950
1960
1970
1980
1990
Yr
2000
2010
2020
2030
Reprinted from Gastroenterology, 138, Davis GL, et al, Aging of hepatitis C virus (HCV)-infected persons in the United
States: a multiple cohort model of HCV prevalence and disease progression, 513-521, Copyright 2010, with
permission from Elsevier.
HCV Life Cycle and DAA Targets
Receptor binding
and endocytosis
Transport
and release
Fusion and
uncoating
ER lumen
(+) RNA
LD
LD
Translation
NS3/4 and
protease
polyprotein
inhibitors
processing
Membranous
web
Virion
assembly
LD
ER lumen
NS5A* inhibitors
*Role in HCV life cycle not well defined
Adapted from Manns MP, et al. Nat Rev Drug Discov. 2007;6:991-1000.
NS5BRNA
polymerase
inhibitors
replication
Nucleoside/nucleotide
Nonnucleoside
Sustained virologic response (SVR) as
Clinical Endpoint
• SVR used as endpoint of successful HCV treatment
– Defined as undetectable serum HCV RNA levels 24 wks after end of treatment
• Achieving SVR results in significant reduction of HCV-associated
complications and mortality[1,2]
SVR better
No SVR better
Genotype 1
P < .0001
Genotype 2
P = .004
Genotype 3
P < .0001
0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
All-Cause Mortality HR (95% CI)
1. Morgan TR, et al. Hepatology. 2010;52:833-844. 2. Backus L, et al. 2010 AASLD. Abstract 213.
HCV Standard of Care Prior to May
2011
 GT1 (most common in US, Europe) least responsive to pegIFN/RBV
PegIFN alfa-2b 1.5 µg/kg/wk +
RBV 800 mg/day for 48 Wks[1]
100
100
82
SVR (%)
80
60
76
80
60
54
PegIFN alfa-2a 180 µg/wk +
Weight-Based RBV (1000 or
1200 mg/day) for 48 Wks[2]
56
46
42
40
40
20
20
0
n = 511
Overall
348
147
GT1
GT2/3
0
n = 453
Overall
298
140
GT1
GT2/3
1. Manns MP, et al. Lancet. 2001;358:958-965. 2. Fried MW, et al. N Engl J Med. 2002;347:975-982.
Suboptimal Virologic Responses
HCV RNA (log10 IU/mL)
8
PegIFN/RBV
7
6
Relapse
Null response
5
4
Breakthrough
2 log10 decline
3
Partial
2
response
Limit of detection
1 Incomplete
0 treatment
0 4 8 12 18 24 30 36 42 48 54 60 66 72 78
Wks
McHutchison JG, et al. N Engl J Med. 2009;361:580-593.
Development of Viral Resistance
Drug-susceptible quasispecies
Drug-resistant quasispecies
Viral Load
Treatment begins
Selection of resistant
quasispecies
Incomplete suppression
 Inadequate potency
 Inadequate drug levels
 Inadequate adherence
 Preexisting resistance
Time
Limitations of PegIFN/RBV
• In GT1/4 slow responders variable results
achieved by extending therapy to 72 wks [1-4]
• Few options available for patients who fail
pegIFN/RBV[5-8]
• SVR rates consistently lower among blacks,
older patients, individuals with advanced
cirrhosis[9,10]
1. Berg T, et al. Gastroenterology. 2006;130:1086-1097. 2. Pearlman BL, et al. Hepatology. 2007;46:1688-1694. 3.
Sanchez-Tapias JM, et al. Gastroenterology. 2006;131:451-460. 4. Buti M, et al. Hepatology. 2010;52:1201-1207. 5.
Poynard T, et al. Gastroenterology. 2009;136:1618-1628. 6. Pearlman BL, et al. AASLD 2009. Abstract 815. 7. Jensen
DM, et al. Ann Intern Med. 2009;150:528-540. 8. Bacon BR, et al. Hepatology. 2009;49:1838-1846. 9. Jacobson IM,
et al. Hepatology. 2007;46:982-990. 10. Huang CF, et al. J Infect Dis. 2010;201:751-759.
Adherence to PegIFN/RBV: Essential
but Challenging
 Retrospective analysis of
pegIFN alfa-2b/RBV trials (N
= 511)[1]
100
SVR (%)
80
63
60
54
53
72
75
40
17
20
n=
0
35
10
24
305
30
50
70
90
Adherence Rate (%)
• Only ~ 60% of US patients
adhere to HCV therapy[2]
• Drug exposure correlates
with SVR; ≥ 80% adherence
correlates with SVR[1,3]
• Patient self-report
overestimates adherence[4]
• Adherence wanes over
time[4]
1. McHutchison JG, et al. Gastroenterology. 2002;123:1061-1069. 2. Mitra D, et al. Value Health. 2010;13:479-486.
3. Raptopoulou M, et al. J Viral Hepat. 2005;12:91-95. 4. Smith SR, et al. Ann Pharmacother. 2007;41:1116-1123.
Limitations of IFN-based therapy
2. Tolerability and acceptance
100 HCV RNA+ Patients
40 Eligible Patients
28 Start Therapy
5 Cures
Ineligible patients,
60%
Eligible patient
refusal, 30%
Patient dropout or
nonresponse, 75%
Modeled on Falck-Ytter Y. Annals 2002.
IL28B Genotype a Strong Predictor of
SVR With PegIFN/RBV in Genotype 1
HCV
Whites (n = 871)
Blacks (n = 191)
Factor Associated With SVR
Hispanics (n = 75)
Odds Ratio (95% CI)
7.3
6.1
IL28B rs12979860
genotype (CC vs TT)
5.6
4.2
Baseline HCV RNA
(< vs ≥ 600,000 IU/mL)
5.1
2.4
3.0
1.1
Baseline fibrosis
(METAVIR F0-F2 vs F3-F4)
4.1
0.1
Ge D, et al. Nature. 2009;461:399-401.
1.0
10.0
Direct-Acting Antiviral Agents
• Directly target HCV
• Improve virological response when combined with pegIFN/RBV
• HCV NS3/4A protease inhibitors (PI) boceprevir and telaprevir
approved by FDA, May 2011[1,2]
– Indicated in combination with pegIFN/RBV for treatment of
GT1 HCV–infected patients who are untreated or who have
failed previous therapy
1. Boceprevir [package insert]. May 2011. 2. Telaprevir [package insert]. May 2011. 3.
Key Factors for Considering Treatment
Candidacy for PI-Based Therapy
Factor
Role
Genotype
 Boceprevir and telaprevir licensed only for patients with genotype 1 HCV
Fibrosis stage
 Individuals with mild or moderate fibrosis have better rates of SVR with PI-based
triple therapy than those with advanced fibrosis or cirrhosis
 SVR rates for individuals with cirrhosis are markedly improved with PI-based therapy
vs pegIFN/RBV alone, but SVR rates are still lower than for individuals with F0-F3
fibrosis
Treatment
experience
 Treatment-naive patients and previous relapsers or partial responders to IFN-based
therapy have excellent response rates with PI-based therapy
 Both previous partial responders and previous null responders have lower SVR rates
with triple therapy than treatment-naive patients or relapsers. Previous null
responders have the lowest SVR rates with triple therapy
Boceprevir and Telaprevir Clinical Trials
• Phase III trials leading to approval
– Boceprevir plus pegIFN/RBV
• SPRINT-2: treatment-naive patients[1]
• RESPOND-2: treatment-experienced patients[2]
– Telaprevir plus pegIFN/RBV
• ADVANCE: treatment-naive patients[3]
• ILLUMINATE: treatment-naive patients[4]
• REALIZE: treatment-experienced patients[5]
1. Poordad F, et al. N Engl J Med. 2011;364:1195-1206. 2. Bacon BR, et al. N Engl J Med. 2011;364:1207-1217. 3.
Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416. 4. Sherman KE, et al. 2010 AASLD. Abstract LB2. 5. Zeuzem S,
et al. N Engl J Med. 2011;364:2417-2428.
Telaprevir Monotherapy and
Development of Resistance
Telaprevir Dosing
8
Patient 1018
6
4
LOD
2
0
Log10 HCV RNA (IU/mL)
Log10 HCV RNA (IU/mL)
8
Telaprevir Dosing
Patient 1002
6
4
LOD
2
0
1
Days
14
HCV RNA (>100 IU/mL)
Wild type
T54A
V36A/M
Kieffer TL, et al. Hepatology. 2007;46:631-639.
1
R155K/T
36/155
A156V/T
36/156
Days
14
Phase III SPRINT-2: Boceprevir +
PegIFN/RBV in GT 1 Tx-Naive Patients
Randomized, placebo-controlled trial
Treatment-naive
patients with
genotype 1 HCV
(2 cohorts:
N = 938
nonblack and 159
black)
PR*
(n = 316,
52)
PR*
(n = 311,
55)
BOC + PR*
(n = 316 nonblack,
52 black)
RVR†
Wk 28
Wk 4
No RVR

Follow-up
PR*
BOC + PR*
(n = 311 nonblack, 55 black)
PR*
(n = 311 nonblack, 52 black)
*BOC 800 mg q8h; pegIFN alfa-2b 1.5 µg/kg/wk; weight-based RBV 600-1400 mg/day.
†Undetectable HCV RNA at Wk 4 of BOC treatment (ie, at Wk 8) and at all subsequent assays.
Poordad F, et al. N Eng J Med. 2011;364:1195-1206.
Wk 72
Wk 48
Follow-up
Follow-up
Follow-up
SPRINT-2: Response Rates According
to Race
4-wk PR → response-guided BOC + PR
4-wk PR → 44-wk BOC + PR
Nonblack Patients
100
48-wk PR
Black Patients
100
P < .001
80
80
68
P = .004
60
40
40
23
20
0
Patients (%)
Patients (%)
67
P = .04
9
n = 211 213 125
SVR
60
53
42
40
23
20
12
8
21 18
37
Relapse
Poordad F, et al. N Eng J Med. 2011;364:1195-1206.
0
22
29
SVR
12
3
17
14
6
2
Relapse
Phase III RESPOND-2: Boceprevir in GT
1 Previous Nonresponders to
PegIFN/RBV
Wk 36
Wk 8
No RVR RVR
Wk 4
Wk 48
Follow-up†
PR*
(n = 162)
Treatmentexperienced
patients with
GT 1 HCV
PR*
(n = 161)
(N = 403)
BOC + PR*
(n = 162)
BOC + PR*
(n = 161)
PR*
(n = 80)
*BOC 800 mg TID; pegIFN alfa-2b 1.5 µg/kg/wk; weight-based RBV 600-1400 mg/day.
†Follow-up for 24 wks after completion of therapy.
Bacon BR, et al. N Engl J Med. 2011;364:1207-1217.
PR*
Follow-up†
Follow-up†
Follow-up†
RESPOND-2: SVR Rates With
Boceprevir-Based Therapy by Previous
Response

SVR rates with boceprevir-based triple therapy higher among previous relapsers vs
previous partial responders to pegIFN/RBV therapy (previous
null responders excluded from study)
– Both groups had higher SVR rates vs pegIFN/RBV alone
100
Previous partial response
SVR (%)
80
75
69
60
40
52
40
29
20
0
Previous relapse
7
n/N = 23/57 72/105
30/58 77/103
BOC RGT
Bacon BR, et al. N Engl J Med. 2011;364:1207-1217.
BOC/PR48
2/29 15/51
PR48
Phase III ADVANCE: Telaprevir +
PegIFN/RBV in GT 1 Tx-Naive Patients

Randomized, placebo-controlled trial
Wk 8
TVR + PR*
(n = 364)
Treatment-naive
patients with
GT 1 HCV
TVR + PR*
(n = 363)
Wk 24
Wk 12
eRVR†: PR*
Wk 72
Wk 48
Follow-up
PR*
eRVR†: PR*
Follow-up
Follow-up
PR*
Follow-up
(N = 1088)
PR*
(n = 361)
*TVR 750 mg q8h; pegIFN alfa-2a 180 µg/wk; weight-based RBV 1000-1200 mg/day.
†eRVR = undetectable HCV RNA at Wks 4 and 12.
Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416.
Follow-up
ADVANCE: Overall SVR and
Relapse Rates
100
P < .0001 for both treatment
arms vs control
80
Patients (%)
T8PR24/48 (n = 364)
T12PR24/48 (n = 363)
PR48 (n = 361)
69
75
60
44
40
28
20
0
n=
250
271
158
SVR
Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416.
n=
9
9
28
27
Relapse
64
REALIZE: Telaprevir in GT1 TreatmentExperienced Patients
Randomized 2:2:1;
stratified by HCV RNA and
previous response
Wk 4
Wk 12
Telaprevir 750 mg q8h
+ PR*
(n = 266)
Patients with GT1 HCV
who previously failed
pegIFN/RBV
Placebo +
PR*
(n = 264)
Wk 16
Wk 48
Placebo +
PR*
PR*
Telaprevir 750 mg q8h
+ PR*
PR*
(N = 632)
Placebo + PR*
(n = 132)
*PegIFN alfa-2a 180 µg/wk + RBV 1000-1200 mg/day.
Zeuzem S, et al. N Engl J Med. 2011;364:2417-2428.
PR*
24-wk
follow-up
for SVR
REALIZE: SVR Rates With TelaprevirBased Therapy by Previous Response

SVR rates with telaprevir-based triple therapy higher among previous relapsers vs
previous partial responders vs null responders to pegIFN/RBV
– All groups had higher SVR rates vs pegIFN/RBV alone
T12/PR48
Previous Relapsers
100
83*
LI T12/PR48
Pbo/PR48
Previous Partial
Responders
Previous Null
Responders
88*
SVR (%)
80
59*
60
54*
40
29*
24
15
20
n/N=
0
33*
121/145
124/141
16/68
29/49
Zeuzem S, et al. N Engl J Med. 2011;364:2417-2428.
26/48
4/27
5
21/72
25/75
2/37
*P < .001 vs Pbo/PR48
Patients Who Are Not Candidates for
PI-Based Therapy
• Patients with previous serious adverse events leading to premature
pegIFN/RBV treatment discontinuation
• Contraindications for boceprevir and telaprevir therapy
– Pregnant women or men whose female partners are pregnant
– Coadministration with other drugs highly dependent on CYP3A4/5 for
clearance and for which elevated plasma concentrations associated with
serious/life-threatening events
– When coadministered with potent CYP3A4/5 inducers where significantly
reduced boceprevir or telaprevir plasma concentrations may be associated
with reduced efficacy
• Safety and pharmacokinetics of the PIs have not been studied in patients
with decompensated cirrhosis or in liver transplant recipients
Resistance to Protease Inhibitors
• Resistance may develop rapidly with protease
inhibitors
• It is ESSENTIAL that patients take pegIFN/RBV
with protease inhibitors
• NEVER dose reduce a protease inhibitor
• Always STOP the protease inhibitor if HCV RNA
begins to increase
Boceprevir Regimens
•
Treatment-naive patients
– 4-wk lead-in period of pegIFN/RBV alone, then triple therapy with BOC 800 mg TID +
pegIFN/RBV for 24-32 wks
• Duration dependent on treatment response*
• Followed by additional 12 wks of pegIFN/RBV alone for slow responders
•
Previous partial responders and relapsers
– 4-wk lead-in period of pegIFN/RBV alone, then triple therapy with BOC 800 mg TID +
pegIFN/RBV for 32 weeks
• Followed by additional 12 wks of pegIFN/RBV alone for slow responders
•
Previous null responders and all cirrhotic patients
– 4-wk lead-in period of pegIFN/RBV alone, then triple therapy with BOC 800 mg TID +
pegIFN/RBV for 44 weeks
*Treatment duration covered in detail in next section.
Boceprevir [package insert]. 2011.
Telaprevir Regimens
• Treatment-naive patients and previous relapsers
– Triple therapy with TVR 750 mg TID + pegIFN/RBV for
12 wks, followed by 12-36 wks of pegIFN/RBV alone
• Duration of pegIFN/RBV dependent on treatment response*
(except cirrhotics may benefit from full 48-wk course)
• Previous partial and null responders
– Triple therapy with TVR 750 mg TID + pegIFN/RBV for
12 wks, followed by 36 wks of pegIFN/RBV alone
*Treatment duration covered in detail in next section.
Telaprevir [package insert]. 2011.
Pros and Cons of Treating vs Deferring
Therapy Once PIs Are Available
Treat
Defer
 Protease inhibitors substantially
increase chance of SVR
 Current regimens complex,
challenging adverse events
 Successful treatment may arrest
progression of liver disease
(including potential for cirrhosis,
HCC, etc)
 Potential for better treatment
options in future, eg, better
response rates, fewer adverse
events, shorter duration
 Many patients already
“warehoused” awaiting DAAs, but
when is the right time to exit the
warehouse?
 Risk of resistance if therapy
fails; impact on future options?
Study 110: Preliminary Data in
HIV/HCV Coinfection
• Higher rates of undetectable HCV RNA at Wks 4 and 12
with telaprevir plus pegIFN/RBV vs pegIFN/RBV alone
– Similar results regardless of use of concurrent ART
Undetectable HCV RNA, Wk 4 (ITT)
Undetectable
HCV RNA (%)
100
80
71
75
64 70
60
40
12
20
0
n/N=
0
5/7
12/16 9/14 26/37
Telaprevir + PR
0/6
0
1/8
0/8
PR
Sulkowski M, et al. 2011 CROI. Abstract 146LB.
5
1/22
ATV/RTV-based ART
Total
100
80 71 75
57
60
Undetectable
HCV RNA (%)
No ART
EFV-based ART
Undetectable HCV RNA, Wk 12 (ITT)
68
40
17
20
0
n/N=
5/7 12/16 8/14 25/37
Telaprevir + PR
1/6
12 12
14
1/8
3/22
PR
1/8
Select DAAs in Clinical Development
Phase I
Phase II
Phase III
Protease Inhibitors
ABT-450
ACH-1625
GS 9451
MK-5172
VX-985
BMS-650032
CTS-1027
Danoprevir
GS 9256
IDX320
Vaniprevir
BI 201335
Boceprevir
Telaprevir
TMC435
Nonnucleoside
polymerase inhibitors
BI 207127
IDX375
ABT-333
ABT-072
ANA598
BMS-791325
Filibuvir
Tegobuvir
VX-759
VX-222
Nucleoside polymerase
inhibitors
NS5A inhibitors
IDX184
PSI-7977
RG7128
A-831
PPI-461
BMS-790052
BMS-824393
CF102
Points to remember
• Incidence is declining, but prevalence of HCVrelated cirrhosis will markedly increase in next
10-20 years
• HCV treatment can induce permanent
remission and reduces mortality and morbidly
• DAAs markedly increases effectiveness of
treatment in difficult to treat patients
(genotype 1, advanced fibrosis, previously
treated and African Americans)